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Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

View ORCID ProfileMartina Milighetti, Yanchun Peng, View ORCID ProfileCedric Tan, Michal Mark, Gayathri Nageswaran, Suzanne Byrne, View ORCID ProfileTahel Ronel, Tom Peacock, View ORCID ProfileAndreas Mayer, Aneesh Chandran, Joshua Rosenheim, Matthew Whelan, Xuan Yao, Guihai Liu, Suet Ling Felce, Tao Dong, Alexander J. Mentzer, Julian C. Knight, Francois Balloux, Erez Greenstein, Shlomit Reich-Zeliger, Corrina Pade, Joseph M. Gibbons, Amanda Semper, Tim Brooks, View ORCID ProfileAshley Otter, Daniel M Altmann, Rosemary J Boyton, Mala K Maini, Aine McKnight, Charlotte Manisty, Thomas A. Treibel, James C. Moon, COVIDsortium Investigators, View ORCID ProfileMahdad Noursadeghi, Benny Chain
doi: https://doi.org/10.1101/2022.11.08.515436
Martina Milighetti
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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  • ORCID record for Martina Milighetti
Yanchun Peng
2MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford; Oxford, UK
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
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Cedric Tan
5UCL Genetics Institute, University College London; London WC1E 6BT, UK
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Michal Mark
6Department of Systems Immunology, Weizmann Institute of Science; Rehovot 7610001, Israel
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Gayathri Nageswaran
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Suzanne Byrne
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Tahel Ronel
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Tom Peacock
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Andreas Mayer
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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  • ORCID record for Andreas Mayer
Aneesh Chandran
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Joshua Rosenheim
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Matthew Whelan
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Xuan Yao
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
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Guihai Liu
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
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Suet Ling Felce
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
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Tao Dong
2MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford; Oxford, UK
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
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Alexander J. Mentzer
4Wellcome Centre for Human Genetics; University of Oxford; Oxford, U.K.
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Julian C. Knight
3Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.
4Wellcome Centre for Human Genetics; University of Oxford; Oxford, U.K.
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Francois Balloux
5UCL Genetics Institute, University College London; London WC1E 6BT, UK
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Erez Greenstein
6Department of Systems Immunology, Weizmann Institute of Science; Rehovot 7610001, Israel
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Shlomit Reich-Zeliger
6Department of Systems Immunology, Weizmann Institute of Science; Rehovot 7610001, Israel
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Corrina Pade
7Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; London E1 4NS, UK
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Joseph M. Gibbons
7Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; London E1 4NS, UK
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Amanda Semper
7Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; London E1 4NS, UK
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Tim Brooks
8UK Health Security Agency; Porton Down, Salisbury, SP4 0JG, UK
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Ashley Otter
8UK Health Security Agency; Porton Down, Salisbury, SP4 0JG, UK
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  • ORCID record for Ashley Otter
Daniel M Altmann
9Department of Immunology and Inflammation, Imperial College London; London SW7 2BX, UK
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Rosemary J Boyton
10Department of Infectious Disease, Imperial College London; London, W12 0NN, UK
11Lung Division, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust; London, UK
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Mala K Maini
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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Aine McKnight
7Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; London E1 4NS, UK
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Charlotte Manisty
12Institute of Cardiovascular Sciences, University College London; London WC1E 6BT, UK
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Thomas A. Treibel
12Institute of Cardiovascular Sciences, University College London; London WC1E 6BT, UK
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James C. Moon
12Institute of Cardiovascular Sciences, University College London; London WC1E 6BT, UK
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Mahdad Noursadeghi
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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  • ORCID record for Mahdad Noursadeghi
Benny Chain
1Division of Infection and Immunity, University College London; London WC1E 6BT, UK
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  • For correspondence: b.chain@ucl.ac.uk
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Abstract

We analyzed the dynamics of the earliest T cell response to SARS-COV-2. A wave of TCRs strongly but transiently expand during infection, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Most epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains, but not with circulating human coronaviruses. Many expanding CDR3s were also present at high precursor frequency in pre-pandemic TCR repertoires. A similar set of early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the pre-infection naïve repertoire. High frequency naïve precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.

One-Sentence Summary High frequency naïve precursors underly the rapid T cell response during the crucial early phases of acute viral infection.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵‡ Full list of the authors and affiliations is given in the Supplementary Materials

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection
Martina Milighetti, Yanchun Peng, Cedric Tan, Michal Mark, Gayathri Nageswaran, Suzanne Byrne, Tahel Ronel, Tom Peacock, Andreas Mayer, Aneesh Chandran, Joshua Rosenheim, Matthew Whelan, Xuan Yao, Guihai Liu, Suet Ling Felce, Tao Dong, Alexander J. Mentzer, Julian C. Knight, Francois Balloux, Erez Greenstein, Shlomit Reich-Zeliger, Corrina Pade, Joseph M. Gibbons, Amanda Semper, Tim Brooks, Ashley Otter, Daniel M Altmann, Rosemary J Boyton, Mala K Maini, Aine McKnight, Charlotte Manisty, Thomas A. Treibel, James C. Moon, COVIDsortium Investigators, Mahdad Noursadeghi, Benny Chain
bioRxiv 2022.11.08.515436; doi: https://doi.org/10.1101/2022.11.08.515436
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Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection
Martina Milighetti, Yanchun Peng, Cedric Tan, Michal Mark, Gayathri Nageswaran, Suzanne Byrne, Tahel Ronel, Tom Peacock, Andreas Mayer, Aneesh Chandran, Joshua Rosenheim, Matthew Whelan, Xuan Yao, Guihai Liu, Suet Ling Felce, Tao Dong, Alexander J. Mentzer, Julian C. Knight, Francois Balloux, Erez Greenstein, Shlomit Reich-Zeliger, Corrina Pade, Joseph M. Gibbons, Amanda Semper, Tim Brooks, Ashley Otter, Daniel M Altmann, Rosemary J Boyton, Mala K Maini, Aine McKnight, Charlotte Manisty, Thomas A. Treibel, James C. Moon, COVIDsortium Investigators, Mahdad Noursadeghi, Benny Chain
bioRxiv 2022.11.08.515436; doi: https://doi.org/10.1101/2022.11.08.515436

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